RheumShorts: New Knees, Lupus Med Switches

Action Points

Note that a study of lupus patients who switched from mycophenolate mofetil to azathioprine or vice versa demonstrated that, in general, the switch was met with improved disease symptomatology and decreased side effects.

Note that another study found that patients with both scleroderma and polymyositis appear to have a greater risk for interstitial lung disease than those with either disease alone.

The news in rheumatology this week included reports on knee replacements in the Dominican Republic, outcomes with scleroderma overlap disease, and reasons for switching maintenance therapy in lupus.

New Knees in the Developing World

Among a group of individuals with arthritis in the Dominican Republic, considerable improvements were seen in activities of various life domains following total knee replacement, according to researchers from Harvard Medical School.

All of the patients also experienced benefits for committed activities, which were those associated with social roles and include paid work, family and child care, and household duties.

In addition, all but one felt they were more able to participate in discretionary activities, which included exercise, hobbies, recreation, and spiritual or religious activities.

Each year in the U.S., more than 600,000 knee arthroplasties are performed, permitting individuals with disabling arthritis to return to normal activities. However, these procedures aren't widely available in countries such as the Dominican Republic, where the per-capita gross domestic product is only about 20% of that in the U.S.

In response to this need, groups of clinicians in the developed world have been undertaking "philanthropic surgical mission trips" to perform the needed surgeries.

"One such program is Operation Walk Boston, which has been offering total knee replacement to economically disadvantaged patients in the Dominican Republic since 2008," Stenquist and colleagues reported.

The group has partnered with physicians at Hospital General de la Plaza de la Salud in Santo Domingo, where each year the physicians implant new knees in about 45 patients.

During its 2013 mission, Operation Walk Boston invited a group of previous recipients to be interviewed, in order to hear about the impact the surgery had on their lives.

Participants reported on an increased ability to perform multiple activities, ranging from getting out of bed and dressing, to working as a house painter, being involved in municipal politics, taking children to the beach, feeding chickens, and attending church services.

Other improvements that were important to patients were in mood and mental health following relief of pain and being better able to sleep and socialize.

"Religion formed the basis of most patients' explanatory model for total knee replacement .... Patients often ascribed their experience of having total knee replacement and enjoying the attendant gains in physical capacity to divine intervention," the researchers noted.

"Knowledge of culturally influenced understanding of disease and treatment is especially important for clinicians working in global health settings, as well as with minority patients in the developed world," they observed.

"As the global burden of musculoskeletal disease increases, it is important to understand the impact of activity limitation on patients' lives in diverse settings, and the potential for surgical intervention to ease the burden of chronic arthritis," they concluded.

Overlap Disease Worse in Scleroderma

Patients with systemic sclerosis who also have features of polymyositis may have worse disease features than those with scleroderma or polymyositis alone, Dutch researchers found.

"The increased prevalence of interstitial lung disease in overlap patients should warrant regular screening for this complication and timely initiation of specific immunosuppressive therapy," the researchers wrote online in Arthritis Research & Therapy.

Previous studies have suggested that survival may be worse and cardiac involvement more pronounced in patients with scleroderma-polymyositis overlap syndrome, but specific disease and outcome details have been lacking.

Therefore, Bhansing's group analyzed data from the Nijmegen Systemic Sclerosis and Myositis cohorts, which include all Dutch patients referred for these conditions.

In the overlap group, mean age at diagnosis was 53, median disease duration was 5 years, and the female-to-male ratio was 1:1.

In the scleroderma-alone group, age was 50, disease duration was 7 years, and the female-to-male ratio was 2:1. In the polymyositis group, age was 51, duration was 3.5 years, and the female-to-male ratio was 1:2.

The overall prevalence of the overlap syndrome was 5.9%.

Along with the greater prevalence of interstitial lung disease in the overlap group, there also was an increased prevalence of decreased lung carbon monoxide diffusion capacity, with all overlap patients having a TLCO below 70% of predicted compared with 75% and 65% of patients with scleroderma and polymyositis, respectively (P=0.001).

Diastolic dysfunction was identified on echocardiography in all groups: in 37% of the overlap patients, 42% of the scleroderma group, and 21% of the polymyositis group, which was not a significant difference. However, they noted that echocardiography, not cardiac MRI, was used for screening.

"Echocardiography lacks specificity to accurately diagnose myocarditis, so the prevalence of this complication could prove to be higher if cardiovascular MRI was performed as well," the researchers noted.

Progressive heart disease was the cause of death in 25% of the overlap patients but in only 10.8% of the scleroderma-alone patients.

Findings on muscle biopsy also were more pronounced in the overlap group, with necrotic muscle fibers being present in 96% compared with 67% of the polymyositis patients.

Lymphocytic infiltrates and other signs of inflammation were more commonly found on the muscle biopsies of the overlap group, although this was not statistically significant.

"Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relationship to pulmonary involvement and mortality in systemic sclerosis-polymyositis overlap patients in order to optimize treatment, increase survival, and improve quality of life," Bhansing and colleagues concluded.

Switching Maintenance Tx in Lupus

Patients with lupus undergoing maintenance therapy with azathioprine or mycophenolate mofetil (Cellcept) tend to switch treatment for different reasons, Canadian researchers reported.

Among patients who switched from azathioprine to mycophenolate, the reasons were disease flare in 85.4% and adverse events in only 12.4%, according to Murray B. Urowitz, MD, and colleagues from the University of Toronto.

Other reasons included the patient's desire for pregnancy, for transplant, or because of financial constraints.

It's been well established that maintenance therapy following induction with cyclophosphamide improves renal outcomes in lupus, but whether azathioprine or mycophenolate is superior has remained controversial.

There are no current guidelines to direct maintenance therapy beyond 3 years, so clinicians face uncertainties when treatment fails or becomes intolerable.

Therefore, Urowitz and colleagues examined the reasons for switching and the effects of doing so in a large cohort of patients seen at the Toronto Lupus Clinic between 2001, when mycophenolate became available for use there, and 2012.

Their cohort included 778 patients, of whom 463 were on azathioprine and 315 were receiving mycophenolate.

During the study period, 16% of patients on azathioprine switched after a mean of 4 years, while 6% switched from mycophenolate after 1.7 years.

Most of the 92 patients who switched were women, and there were 108 switches overall. Participants' age at diagnosis was 26, disease duration at the time of medication switch was 10 years, and lupus disease activity score was 10.5 at the time medication was changed.

A total of 89 switches from azathioprine to mycophenolate occurred. Among the specific reasons for switching from azathioprine were renal flares in 55.3% of those who changed medications, systemic flares in 15.8%, central nervous flares in 6.6%, and other organ flares in smaller numbers of patients.

Among the side effects in this group were liver enzyme abnormalities and gastrointestinal disturbances, and in 81.8% the switch resolved the adverse effect.

A switch from mycophenolate to azathioprine was reported in 19 instances. In patients with treatment failure, most involved systemic flares or renal flares, though the numbers were small (two and one, respectively).

The most common side effect was gastrointestinal intolerance, while small numbers had rashes, fatigue, and leukopenia.

Statistically significant improvements were seen in disease activity scores 6 months after the treatment changes when the reason had been treatment failure (11.2 versus 9.1, P<0.0001), with laboratory measures being the most prominent area of improvement. In these patients, there also was a significant decrease in steroid dose after the medication was changed (24.9 mg/day versus 18.3 mg/day, P=0.0002).

No changes in disease activity scores were seen 6 months after the switch when the reason had been adverse events, pregnancy, or other causes. In 79% of cases, the side effects resolved after the change in treatment.

A limitation of the study was the low number of patients who switched from mycophenolate to azathioprine.

Stenquist and colleagues were supported by the National Institutes of Health and Harvard Medical School.

Urowitz and colleagues' lupus clinic was supported by the Smyth Foundation and University Health Network.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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